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1.
Drug Chem Toxicol ; 46(4): 692-698, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35670081

RESUMO

This study is aimed at establishing the outcome of RSTI exposure to acetaminophen based on a decision tree algorithm for the first time. This study used the National Poison Data System (NPDS) to conduct a six-year retrospective cohort analysis, which included 4522 individuals. The patients had a mean age of 26.75 ± 16.3 years (1-89). 3160 patients (70%) were females. Most patients had intentional exposure to acetaminophen. Almost all the patients had acetaminophen exposure via ingestion. In addition, 400 (8.8%) experienced major outcomes, 1500 (33.2%) experienced moderate outcomes, and 2622 (58%) of the patients experienced mild ones. The decision tree model performed well in the training and test groups. In the test group, the accuracy was 0.813, precision of 0.827, recall being 0.798, specificity 0.898, and an F1 score 0.80. In the training group, accuracy was 0.831, recall was 0.825, precision was 0.837, specificity was 0.90, and F1 score was 0.829. Our results showed that serum liver enzymes being present at elevated levels (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) greater than 1000 U/L followed by ALT, AST between 100 and 1000 U/L), prothrombin time (PT) prolongation, bilirubin increase, renal failure, confusion, age, hypotension, other coagulopathy (such as partial thromboplastin time (PTT) prolongation), acidosis, and electrolyte abnormality were the effective factors in determining the outcomes in these patients. The decision tree algorithm is a dependable method for establishing the prognosis of patients who have been exposed to RSTI acetaminophen and can be used throughout the patients' hospitalization period.


Assuntos
Analgésicos não Narcóticos , Doença Hepática Induzida por Substâncias e Drogas , Venenos , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Masculino , Acetaminofen/efeitos adversos , Analgésicos não Narcóticos/efeitos adversos , Estudos Retrospectivos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Algoritmos , Árvores de Decisões , Ingestão de Alimentos
2.
Toxicol Ind Health ; 39(7): 364-373, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37207345

RESUMO

Carbon tetrachloride (CCl4) is a potent liver toxin. Diclofenac (Dic), leading adverse effects on the liver, is used among the employees of the industries that use CCl4. The increased use of CCl4 and Dic in industrial workers has prompted us to investigate their synergistic effect on the liver using male Wistar rats as a model. Male Wistar rats were divided into seven groups (n = 6), and the exposure was by intraperitoneal injection for 14 days as follows. Group 1: Control, 2: Olive oil, 3: CCl4 (0.8 mL/kg/day (3 times per week)), 4: Normal saline, 5: Dic (1.5 mg/kg/day per day), 6: Olive oil with normal saline, 7: CCl4 (0.8 mL/kg/day (3 times per week)) and Dic (1.5 mg/kg/day daily). At the end of day 14, the heart blood was collected to measure the liver enzymes, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), blood alkaline phosphatase (ALP), albumin (ALB), direct bilirubin, and total bilirubin. A pathologist examined the liver tissue. Prism software was used to analyze data using ANOVA and Tukey statistical tests. ALT, AST, ALP, and Total Bilirubin enzymes were increased significantly in the co-administered CCl4 and Dic group, while the ALB levels decreased (p < 0.05). The histological findings reported liver necrosis, focal hemorrhage, adipose tissue change, and lymphocytic portal hepatitis. In conclusion, using Dic while exposed to CCl4 may exacerbate hepatotoxicity in rats. Therefore, it is suggested that more severe restrictions and safety regulations be placed on using CCl4 in the industry, and caution is advised to these industry workers to use Diclofenac.


Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Ratos , Masculino , Animais , Ratos Wistar , Tetracloreto de Carbono/toxicidade , Diclofenaco/toxicidade , Azeite de Oliva/farmacologia , Solução Salina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fígado , Bilirrubina , Transaminases/farmacologia
3.
Bratisl Lek Listy ; 124(9): 690-698, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37635667

RESUMO

One of the important issues in urban areas is air pollution which causes respiratory disorders. A significant association between exposure to inhaled particulate matter (PM), mainly ultrafine particles, and increased neurological and pulmonary morbidity and mortality was observed in some research. This study aimed to demonstrate the relation between multi-wall carbon nanotubes (MWCNTs) inhalation and the carcinogenic effect of these materials in the brain and lungs. For this purpose, we investigated gene expression in rat brain and lung tissues induced by exposure to MWCNTs. Rats were exposed to MWCNTs in diameters of 10 and 100 nm (pure and impure) at a concentration of 5 mg/m3. Exposure was done through a whole-body exposure chamber for 5 h/day, 5 days/week for 14 days. After exposure, both brain and lung tissues were isolated to evaluate certain gene expressions including Bax, Bcl2, Rac1, Tp53, Mmp12, and Arc. The results showed that exposure to impure and pure MWCNTs (10 and 100 nm) at a concentration of 5 mg/m3 causes up-regulation or down-regulation of some of these genes. The results suggest that impure and pure MWCNTs (10 and 100 nm) can increase the risk of central nervous system disorders such as Alzheimer's disease and increase the risk of carcinogenesis in the lung tissues of rats exposed to MWCNTs (Tab. 2, Fig. 2, Ref. 64). Text in PDF www.elis.sk Keywords: multi-wall carbon nanotube, inhalation, gene expression, carcinogenicity, brain, lung.


Assuntos
Nanotubos de Carbono , Neoplasias , Animais , Ratos , Nanotubos de Carbono/toxicidade , Apoptose , Encéfalo , Pulmão , Genes Neoplásicos
4.
J Res Med Sci ; 28: 84, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38510785

RESUMO

Background: Previous research has emphasized the importance of efficient ventilation in suppressing COVID-19 transmission in indoor spaces, yet suitable ventilation rates have not been suggested. Materials and Methods: This study investigated the impacts of mechanical, natural, single-sided, cross-ventilation, and three mask types (homemade, surgical, N95) on COVID-19 spread across eight common indoor settings. Viral exposure was quantified using a mass balance calculation of inhaled viral particles, accounting for initial viral load, removal via ventilation, and mask filtration efficiency. Results: Results demonstrated that natural cross-ventilation significantly reduced viral load, decreasing from 10,000 to 0 viruses over 15 minutes in a 100 m2 space by providing ~1325 m3/h of outdoor air via two 0.6 m2 openings at 1.5 m/s wind speed. In contrast, single-sided ventilation only halved viral load at best. Conclusion: Natural cross-ventilation with masks effectively suppressed airborne viruses, lowering potential infections and disease transmission. The study recommends suitable ventilation rates to reduce COVID-19 infection risks in indoor spaces.

5.
J Recept Signal Transduct Res ; 42(5): 495-502, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35473566

RESUMO

OBJECTIVE: The effect of thyroid hormone (TH) on cancers was proposed more than 100 years ago; however, conclusions are conflicting. THs are precisely regulated at tissue and cellular levels. It seems that this regulation is altered in cancers. Thyroid hormone receptor beta (TRß) has anti-proliferative and tumor-suppressive effects in many cancer cells. Therefore, we decided to investigate thyroid hormone receptor beta (THRB) expression and activation by the selective agonist, GC-1, on tumor growth in a syngeneic mouse model of colorectal cancer (CRC) and colon cell lines. METHODS: In vitro cell viability assay using MTT analysis, cell cycle analysis by PI staining, and FACS analysis were performed. In vivo tumor growth measurements were carried out by caliper and [18F] Fluoro-2-deoxy-2-D-glucose (FDG) - PET imaging. Gene expressions were determined using quantitative-PCR. RESULTS: Some concentrations of GC-1 had a marked negative effect on the cell viability of colorectal cell lines. Cell cycle analysis showed that the anti-proliferative effect of GC-1 may not result from cell cycle arrest or apoptosis. Tumor growth analysis in mice harboring colorectal tumor showed that GC-1 treatment for 8 d profoundly inhibited tumor growth and 18FDG uptake. THRB expression was decreased in mice tumor; however, it was upregulated following GC-1 administration. CONCLUSIONS: Our results showed that specific activation of TRß by GC-1 had negative effect on tumor growth and restored its gene expression in tumors of CRC mice model.


Assuntos
Neoplasias Colorretais , Receptores beta dos Hormônios Tireóideos , Acetatos , Animais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Fluordesoxiglucose F18 , Glucose , Camundongos , Fenóis , Receptores beta dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/metabolismo , Hormônios Tireóideos
6.
J Emerg Med ; 62(6): 783-788, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35296394

RESUMO

BACKGROUND: Approximately two-thirds of patients discharged from an emergency department (ED) are prescribed at least one medication. Prescription clarification by outpatient pharmacies for ED patients can lead to delays for patients and added workload. OBJECTIVES: This study aims to describe prescriptions requiring clarification prior to being dispensed by an outpatient pharmacy for patients recently discharged from an ED. METHODS: This study was conducted at an urban, 61-bed academic ED. Prescription clarification forms were used to identify common causes for outpatient pharmacies to contact the ED to clarify prescriptions prior to dispensation. Clarification types were reviewed and classified. Descriptive statistics were used to present the classification types. RESULTS: There were 1278 documented calls to the ED for prescription clarification that were classified as clarification of directions for use (611, 47.7%), insurance or affordability issues (182, 14.2%), dose (172, 13.4%), medication availability (126, 9.8%), lost or missing prescription (93, 7.3%), patient allergy or adverse event (62, 4.8%), duplication in therapy (17, 1.3%), and clarification of medication ordered (17, 1.3%). When grouped into provider, system, or patient-related issues, provider issues were noted to be most frequent clarifications (862 clarifications, 67.3%), followed by system issues (325 clarifications, 25.4%), and finally, patient-related issues (93 clarifications, 7.3%). CONCLUSIONS: Clarification of directions for use, insurance or affordability issues, and clarification of the dose were the most common reasons that outpatient pharmacies contacted an ED regarding a prescription for a recently discharged patient.


Assuntos
Farmácias , Farmácia , Prescrições de Medicamentos , Serviço Hospitalar de Emergência , Humanos , Alta do Paciente
7.
Toxicol Appl Pharmacol ; 429: 115681, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34416225

RESUMO

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.


Assuntos
Fontes de Energia Elétrica/efeitos adversos , Saúde Global , Intoxicação por Chumbo/epidemiologia , Ayurveda/efeitos adversos , Dependência de Ópio/epidemiologia , Ópio/efeitos adversos , Ferimentos por Arma de Fogo/epidemiologia , Adolescente , Adulto , Quelantes/uso terapêutico , Criança , Pré-Escolar , Contaminação de Medicamentos , Medicina Baseada em Evidências , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Intoxicação por Chumbo/diagnóstico , Intoxicação por Chumbo/tratamento farmacológico , Masculino , Exposição Ocupacional/efeitos adversos , Dependência de Ópio/diagnóstico , Prognóstico , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , Ferimentos por Arma de Fogo/diagnóstico
8.
Drug Dev Ind Pharm ; 47(8): 1290-1301, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34620021

RESUMO

OBJECTIVE: Considering the limitations of conventional risperidone (RSP) therapies, the present research characterizes the usefulness of multivesicular liposomes (MVLs) as an efficient controlled-release carrier for this widely used antipsychotic drug, to be employed for the treatment of schizophrenia. METHODS: A 23 full factorial design based on three independent variables was implemented to plan the experiments: the molar ratios of lipid to the drug, triolein to phospholipid, and cholesterol to phospholipid. The impacts of these parameters on the risperidone encapsulation efficiency and its release pattern within the first 24 and 48 h were investigated as dependent variables. Then, the optimized liposomal system was further in-depth analyzed in terms of size, morphological and structural features, release profile over 15 days, biocompatibility, and stability. RESULTS: Optimized formulation parameters gave rise to MVLs possessing a spherical morphology with a median diameter of about 8 µm, a relatively narrow size distribution (span value of 1.49), and an encapsulation efficiency of 57.6%. These carriers not only exhibited a sustained-release behavior in vitro, lasting until the end of the 15 days but also underwent a negligible change in their size and RSP incorporation over two months at refrigerator condition. Furthermore, in vitro cytotoxicity and hemolysis assessments revealed that the optimized MVL formulation is biocompatible. CONCLUSION: This study revealed the potential of MVLs as a promising system for the delivery of RSP and could open a new vista for the successful management of schizophrenia.


Assuntos
Lipossomos , Risperidona , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Lipossomos/química , Tamanho da Partícula , Fosfolipídeos
9.
MMWR Morb Mortal Wkly Rep ; 69(32): 1070-1073, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32790662

RESUMO

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.


Assuntos
Higienizadores de Mão/intoxicação , Metanol/intoxicação , Adulto , Idoso , Arizona/epidemiologia , Ingestão de Alimentos , Feminino , Higienizadores de Mão/química , Humanos , Masculino , Metanol/análise , Pessoa de Meia-Idade , New Mexico/epidemiologia , Intoxicação/epidemiologia , Intoxicação/mortalidade , Adulto Jovem
10.
J Food Sci Technol ; 57(4): 1430-1438, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32180639

RESUMO

Detecting meat adulteration for quality control and accurate labeling is important and needs convenient analytical methods. This study aimed to investigate and compare the application of the transmission and ATR approaches of FTIR followed by principal component analysis (PCA) to not only discriminate between chicken and beef meat but also quantizing chicken portion of mixtures. Two different approaches are presented; spectra preprocessing with focus on wavenumber region of 1700-1071 cm-1, and no preprocessed where PCA was applied on the whole spectra range of mid-FTIR. The results suggest that applying PCA on specified preprocessed spectra could detect hidden relationships between variables in chicken and beef in both approaches. PCA successfully clustered these kinds of meats when applied on transmission mode spectra without any preprocessing treatment, while applying it on ATR mode's raw spectra failed to cluster them. Additionally, the preprocessed ATR-FTIR spectrum was used to prepare regression models by Partial Least Square Regression (PLS-R) and artificial neural networks (ANN) for predicting presence and percentage of chicken meat in the beef meat mixture. The results demonstrated the superiority of ANN over PLS-R in this assessment with an R2 of 0.999.

11.
Analyst ; 144(19): 5810-5828, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31469152

RESUMO

Fourier transform infrared (FTIR) spectroscopy is a well-known method of analysis, with various applications, including promising potential for analyzing biological samples. In the bio-spectroscopy of cells, Mie scattering may increase, which then causes spectral distortion, due to the similarity of cell size with the IR medium-wavelength. These changes make the spectrum unreliable. In previous scattering elimination studies, questionable estimations were considered. For instance, all cells were considered as spherical objects or cell size was estimated randomly. In an attempt to provide the best equation based on the natural existence of cells for the FTIR Mie scattering correction, we examined the actual biological data of cells - as opposed to those yielded from mathematical manipulations. So five biological factors: cell size, shape, granularity, circularity, and edge irregularities, for each cell line were considered as factors which cause scattering. For measuring cell size, roundness and edge irregularity, microscopy images were obtained and processed. For evaluating cell line granularity, flow cytometry was used. Finally, by including these factors, an algorithm was designed. To assess the accuracy of the proposed algorithm, the trypsinized cell spectrum was considered as the high scattering spectrum. Cells were also cultured on a MirrIR slide, and their ATR-FTIR spectrum was considered as the minimum scattering spectrum. The algorithm using the abovementioned five characteristics was used for 13 different cell lines, and in some cases the corrected spectrum demonstrated more than 97% resemblance with the ATR spectra of the same cells. A comparison between the results of this algorithm with the Bassan et al. (2017) algorithm for scattering correction that is freely available on the Internet was then conducted on two different cell lines, clearly showing the advantages of our algorithm, in terms of accuracy and precision. Therefore, this method can be viewed as a more suitable solution for scattering correction in cell investigations.


Assuntos
Linhagem Celular Tumoral , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Algoritmos , Linhagem Celular Tumoral/química , Linhagem Celular Tumoral/citologia , Humanos , Raios Infravermelhos , Espalhamento de Radiação
12.
J Pediatr ; 196: 314-317.e1, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29395180

RESUMO

A 17-month-old child presented with hypertension, fussiness, constipation, and arthralgia due to mercury toxicity from a skin-lightening cosmetic used by her mother and grandmother. Blood mercury level was 26 mcg/L and urine level was 243 mcg/g creatinine. She was chelated with succimer. The home was contaminated and needed remediation.


Assuntos
Quelantes/uso terapêutico , Intoxicação por Mercúrio/diagnóstico , Preparações Clareadoras de Pele/efeitos adversos , Succímero/uso terapêutico , Recuperação e Remediação Ambiental/métodos , Feminino , Humanos , Lactente , Mercúrio/sangue , Mercúrio/urina , Intoxicação por Mercúrio/tratamento farmacológico , Intoxicação por Mercúrio/etiologia
13.
Prep Biochem Biotechnol ; 48(10): 961-967, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30461361

RESUMO

The "bispecifics" market improved over the past decade due to the development of many technological platforms including bispecific T cell engagers (BiTEs). The approval of blinatumomab, the most advanced bispecific T-cell engager (BiTE) in clinical trials, can be a significant milestone in the development of bispecific antibodies. Both Chinese hamster ovary (CHO) cells and E. coli strain are considered as the most widely used hosts for the large-scale production of therapeutic monoclonal antibodies. Since both of the economic and qualitative aspects of protein production are important in industry, selection of a suitable protein expression system is very critical. The BsAb gene was cloned into the expression vectors FC550A-1, pcDNA3.1 (+), and PET22b and 6 × His-tagged BsAb then purified on a Ni-NTA chromatography column. Both SDS-PAGE and Western blotting analysis of the purified protein demonstrated that blinatumomab was successfully expressed as a 55 kDa in both expression systems. The antigen-binding properties of blinatumomab were compared in the mammalian system versus Escherichia coli. The results showed that the purified antibody from a mammalian expression system has better binding activity than the one from E. coli host.


Assuntos
Anticorpos Biespecíficos/biossíntese , Anticorpos Biespecíficos/química , Anticorpos Biespecíficos/isolamento & purificação , Escherichia coli , Expressão Gênica , Animais , Células CHO , Cricetulus , Escherichia coli/genética , Escherichia coli/metabolismo
14.
J Exp Ther Oncol ; 12(1): 1-7, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28472558

RESUMO

OBJECTIVE: Cisplatin resistance development is a major obstacle in ovarian cancer treatment. One of the most important mechanisms underlying cisplatin resistance is drug detoxification by glutathione. In the present study, the importance of initial or repeated exposure to cisplatin in glutathione dependent resistance was investigated. To this purpose, some cisplatin sensitive and resistant variants of human ovarian cancer cell lines providing an appropriate range of cisplatin sensitivity were selected. Clonogenic survival assay was performed to evaluate cisplatin resistance and intracellular contents of reduced (GSH) and oxidized (GSSG) glutathione were analyzed using an HPLC method. Our results indicated that the intracellular GSH and GSSG concentrations were nearly equal in A2780 and A2780CP cells, while the A2780CP cells showed 14 times more resistance than the A2780 cells after initial exposure to cisplatin. A2780-R1 and A2780-R3 cells which have been repeatedly exposed to cisplatin also showed no significant difference in glutathione content, even though A2780-R3 was about two times more resistant than A2780-R1. Moreover, intracellular GSH/GSSG ratio decreased in the resistant cells, reflecting a shift towards a more oxidizing intracellular environment indicative of oxidative stress. CONCLUSION: As a conclusion, it seems that although the intracellular glutathione concentration increases after repeated exposure to cisplatin, there is no clear correlation between the intracellular GSH content in ovarian cancer cells and their resistance to cisplatin neither after initial nor after repeated exposure to this drug.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Glutationa/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Dissulfeto de Glutationa/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Células Tumorais Cultivadas
15.
J Exp Ther Oncol ; 12(1): 25-34, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28472561

RESUMO

OBJECTIVE: Breast cancer is one of the most frequent cancers in women. Although there are many treatment protocols for this disease, there are still many patients who do not respond satisfactorily to the current treatment protocols. A better understanding of the nature of the tumor cells might provide a guide for better therapeutic procedures. In this study, the effect of metabolic stress was assessed on the human adenocarcinoma MCF-7 cell line. The cells were seeded in culture plates and after reaching log phase of their growth, cells were exposed to phenol red free-media supplemented with 10%, 0.5%, 0.25% and 0% charcoal-treated serum for 1 to 6 consecutive days. At 24-hour intervals, the cells' ability to proliferate (trypan blue assay), cells mitochondrial content (MTT assay) and intracellular protein content (SRB assay) was assessed. In each day of the study, the cells were released in complete media containing 10% serum for 24 hours and the effect of release was observed on cells. This study showed reduced basal growth rate and proliferation in response to harsh environmental conditions. Protein content of the cells also decreased. Mitochondrial content/activity of the cells however did not decrease, but instead a relative increase was observed at some time points. Releasing the cells caused increased cell proliferation in media with up to 0.5% serum, with an increase in intracellular protein content, although no significant mitochondrial function increase was observed. The results of this study confirm the adaptation of MCF-7 cells to environmental harsh conditions.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Esteroides/metabolismo , Estresse Fisiológico/fisiologia , Adenocarcinoma/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Humanos , Células MCF-7 , Mitocôndrias/patologia , Proteínas/metabolismo
16.
J Emerg Med ; 50(1): 143-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26409675

RESUMO

BACKGROUND: Behavioral health (BH)-related visits to the emergency department (ED) by older adults are increasing. This population has unique challenges to providing quality, timely care. OBJECTIVE: To characterize older adults with BH-related ED visits and determine risk factors associated with prolonged length of stay (LOS) and adverse events (AEs). METHODS: We performed a retrospective electronic health record review of all patients ≥65 years who presented to our ED from September 2011 to August 2012 for BH-related complaints. Sociodemographic, clinical, and utilization data were tested for association with LOS and AE. RESULTS: The 213 elder BH patients represented 4% of the 5267 total elder visits during the study period. Median age was 75 (interquartile range [IQR] 70-82); largely white (84.5%), female (58.7%), and non-Hispanic (69.5%). There was a median of two comorbidities (IQR 1-3), and 46.9% were cognitively impaired. Most (71.5%) were being evaluated on an involuntary basis. Median LOS was 16.2 h (IQR 9.7-29.7). Increased LOS was associated with involuntary status (12.4 h, 95% confidence interval [95% CI] 6.4-18.4); use of restraints (11.9 h, 95% CI 5.7-18.2); and failed discharge (28.8 h, 95% CI 21.2-36.6). For every 10 additional hours in the ED, the risk for an AEs (p = .002) or potential AEs (p = .01) increased 20%. CONCLUSION: Elderly ED patients with BH complaints had high rates of cognitive impairment and multiple comorbidities. LOS was prolonged, and there were multiple contributing factors including involuntary status, chemical or physical restraint, and failed discharge. Patients with longer LOS were at increased risk of an AE or potentially AEs.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Transtornos Mentais/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Logísticos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
18.
South Med J ; 107(3): 150-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24937331

RESUMO

OBJECTIVE: The goal of this study was to analyze trends in the annual rates of reported medical outcomes of cottonmouth (Agkistrodon piscivorus) snakebites in the United States, published in the annual reports of the American Association of Poison Control Centers in the course of 29 years. METHODS: This was a retrospective analysis of medical outcomes for cottonmouth snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by cottonmouths. Negative binomial regression was used to examine trends in annual rates. RESULTS: From 1985 through 2011, after controlling for the availability of CroFab, the annual incidence rate of cottonmouth snakebites causing no effect decreased significantly by 7.3%/year (incidence rate ratio [IRR] 0.927, 95% confidence interval [CI] 0.885-0.970), the incidence rate of minor outcomes did not change significantly (IRR 0.989, CI 0.974-1.006), the incidence rate of moderate outcomes increased significantly by 2.3%/year (IRR 1.023, CI 1.004-1.042), and the incidence rate of major outcomes did not change significantly (IRR 0.987, CI 0.935-1.041). One fatality was reported in 2011. CONCLUSIONS: Annual rates of cottonmouth snakebites producing no effects decreased significantly, those producing minor outcomes did not change significantly, those producing moderate outcomes increased significantly, and those producing major outcomes did not change significantly, from 1985 through 2011.


Assuntos
Agkistrodon , Mordeduras de Serpentes/epidemiologia , Animais , Humanos , Incidência , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
19.
Sci Rep ; 14(1): 14484, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914713

RESUMO

Among the myriad of nanoparticles, silica nanoparticles (SiO2NPs) have gained significant attention since they are extensively produced and used across several kinds of industries. Because of its widespread usage, there has been increasing concern about the potential health effects. This study aims to evaluate the effects of SiO2NPs on Interleukin-6 (IL-6) gene expression in human lung epithelial cell lines (A549). In this study, A549 cells were exposed to SiO2NPs at concentrations of 0, 1, 10, 50, 100, and 200 µg/mL for 24 and 48 h. The IL-6 gene expression was assessed using Real-Time RT-PCR. Additionally, the impact of SiO2NPs on the viability of A549 cells was determined by MTT assay. Statistical analysis was performed using GraphPad Prism software 8.0. MTT assay results indicated a concentration-dependent impact on cell survival. After 24 h, survival decreased from 80 to 68% (1-100 µg/mL), rising to 77% at higher concentrations. After 48 h, survival dropped from 97 to 80%, decreasing to 90% at higher concentrations. RT-PCR showed a dose-response relationship in cellular toxicity up to 10 µg/mL. At higher concentrations, there was increased IL-6 gene expression, mitigating SiO2NP-induced cytotoxic effects. The study shows that the viability and proliferation of A549 cells are impacted by different SiO2NPs concentrations. There may be a potential correlation between IL-6 gene expression reduction and a mechanism linked to cellular toxicity. However, at higher concentrations, an unknown mechanism increases IL-6 gene expression, reducing SiO2NPs' cytotoxic effects. These effects are concentration-dependent and not influenced by exposure times. Further investigation is recommended to determine this mechanism's nature and implications, particularly in cancer research.


Assuntos
Sobrevivência Celular , Interleucina-6 , Nanopartículas , Dióxido de Silício , Humanos , Dióxido de Silício/toxicidade , Dióxido de Silício/química , Células A549 , Nanopartículas/toxicidade , Nanopartículas/química , Interleucina-6/metabolismo , Interleucina-6/genética , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos
20.
Toxicon ; 244: 107775, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782188

RESUMO

Patients occasionally present with reports of ocular exposure to fluids from rattlesnakes, claiming or suspecting the substance to be venom. This study set out to evaluate and characterize reported cases of suspected venom-induced ophthalmia in humans. A retrospective review of rattlesnake exposures reported to the Arizona Poison and Drug Information Center over a 24-year period was conducted for ocular exposures. Recorded information included patient demographics, clinical course, laboratory results, and treatments. Documentation regarding interactions between patients and snakes was reviewed by Arizona Poison and Drug Information Center herpetologists to evaluate what substance was expelled from the snake resulting in ocular exposure. Our review of rattlesnake encounters found a total of 26 ocular exposure cases. Patient demographics were largely intentional interactions and involved the male sex. Symptoms ranged from asymptomatic to minor effects with 46.2% managed from home and treated with fluid irrigation. A review of cases by herpetologists concluded the exposure patients commonly experienced was to snake musk. Kinematics of venom expulsion by rattlesnakes conclude the venom gland must be compressed, fangs erected to ≥60o, and fang sheath compressed against the roof of the mouth for venom expulsion. Evidence suggests the chance of venom "spitting" by rattlesnakes is close to zero. Rattlesnakes are documented to forcefully expel airborne malodorous "musk" defensively. An important distinction to remember is musk has a foul odor and is usually colorless, while venom is comparatively odorless and yellow. Rattlesnake venom-induced ophthalmia is a rare event as venom expulsion requires the kinematics of feeding or defensive bites. If the rattlesnake is not in the process of biting or otherwise contacting some other object with its mouth, it is more biologically plausible patients are being exposed to snake musk as a deterrent. Whether it's venom or musk, topical exposure to the eyes should prompt immediate irrigation.


Assuntos
Venenos de Crotalídeos , Crotalus , Mordeduras de Serpentes , Animais , Arizona , Humanos , Masculino , Estudos Retrospectivos , Feminino , Venenos de Crotalídeos/toxicidade , Adulto , Pessoa de Meia-Idade , Adolescente , Idoso , Criança , Olho/efeitos dos fármacos , Adulto Jovem , Centros de Controle de Intoxicações
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